title: Phospholipase D1 is specifically required for regulated secretion of von Willebrand factor from endothelial cells.
abstract: Endothelial cells regulate thrombosis, hemostasis, and inflammatory responses by supplying the vasculature with several factors that include procoagulant von Willebrand factor (VWF) and fibrinolytic tissue-type plasminogen activator (tPA). Both proteins can be secreted in a Ca(2+)-regulated manner after endothelial activation but exhibit opposing physiologic effects. In search for factors that could modulate endothelial responses by selectively affecting the secretion of procoagulant or anticoagulant proteins, we identify here phospholipase D1 (PLD1) as a specific regulator of VWF secretion. PLD1 is translocated to the plasma membrane upon stimulation of endothelial secretion, and this process correlates with the generation of phosphatidic acid (PA) in the plasma membrane. Histamine-evoked secretion of VWF, but not tPA, is inhibited by blocking PLD-mediated production of PA, and this effect can be attributed to PLD1 and not PLD2. Thus, different mechanisms appear to control the agonist-induced secretion of VWF and tPA, with only the former requiring PLD1.
authors.affiliation: Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Münster, Münster, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Disse
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vitale
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Bader
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism*; D004789:Enzyme Activation; D005089:Exocytosis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010739:Phospholipase D / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013379:Substrate Specificity; D020302:Weibel-Palade Bodies / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D034741:RNA, Small Interfering; D014841:von Willebrand Factor; D010739:Phospholipase D; C106801:phospholipase D1; D010960:Plasminogen Activators